Potentiation of sensory tachykininergic and parasympathetic cholinergic transmission by epidermal growth factor.
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Acetylcholine↗
Biomedical subjects
M D Hollenberg
Publications and source records attributed to M D Hollenberg.
Role of the amino- and carboxyl-terminal domains of thrombin receptor-derived polypeptides in biological activity in vascular endothelium and gastric smooth muscle: evidence for receptor subtypes.
Using guinea pig gastric longitudinal muscle (GLM) and rat gastric longitudinal muscle (RLM) contractile assays and a rat aortic ring (RA) endothelium-dependent relaxation assay, we have examined the biological activities of a number of human and rat thrombin receptor-derived polypeptides (TRPs) modified at amino-terminal and carboxyl-terminal residues. Our study focused primarily on the human pentapeptide [S42FLLR46 (P5)], previously shown to retain full thrombin-like activity. Whereas N-acetylation (N-acetyl-P5) abolished biological activity in the GLM and RA assays, amidation or esterification of the carboxyl-terminal carboxyl group [P5-NH2, P5-OCH3, or S42FLLRNP48-NH2 (P7-NH2)] enhanced peptide potency by about 10-fold in both the GLM and RA assays, compared with the unmodified TRPs (P5 and P7). Removal from P5 of either the amino-terminal hydroxyl group of serine (to yield A42FLLR46) or both the amino-terminal hydroxyl group and the primary amino group of P5 [to yield propionyl-F43LLR46 (Pr-P4)] produced peptides that were active in both the GLM and RA assays. Substitution of the carboxyl-terminal guanidinium group of P5 with a less basic primary amino acid residue (S42FLLK46) resulted in a peptide with a lower potency than that of P5 in the GLM and RA assays, whereas substitution of D-arginine for L-arginine at the carboxyl terminus abolished biological activity. Substitution of norleucine for arginine (S42FLLNorleuN) resulted in a peptide active in the GLM but not in the RA assay. For selected agonists (Pr-P4, P5, P7, and P7-NH2), the potencies in the GLM and RA assays, relative to that of P5, differed; for the GLM the order was P7-NH2 > P7 > P5 congruent to Pr-P4, whereas for the RA the order was P7-NH2 > or = Pr-P4 >> P5 > or = P7. Data comparable to those obtained with the GLM assay were also obtained with a RLM assay, wherein the potency series was P7-NH2 > P7 > P5. The relative potencies of pentapeptides based on the rat receptor sequence [SFFLR (Ra-P5), SFFLR-NH2 (Ra-P5-NH2), and SFFLRNP (Ra-P7)] differed in the RLM and RA assays. In the RLM the order was Ra-P5-NH2 > P7-NH2 > P5-NH2 > Ra-P7 = P7 > P5 = Ra-P5, whereas in the RA the relative potency series was P7-NH2 > P5-NH2 > Ra-P5-NH2 > Ra-P7 > P5 > or = P7 > Ra-P5.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acid Sequence↗
Distinct signal transduction pathways for angiotensin-II in guinea pig gastric smooth muscle: differential blockade by indomethacin and tyrosine kinase inhibitors.
In guinea pig gastric longitudinal (LM) and circular (CM) muscle strips, angiotensin-II (Ang-II) caused a concentration-dependent contraction that required extracellular calcium and that could not be attributed to the secondary release of agonists from neural elements. Contractions in both the LM and CM were blocked by the Ang-II AT1 receptor antagonist, Losartan (DuP 753, pA2 9.1) but not by the AT2 antagonist, PD 123319. However, in the LM preparation, indomethacin (3 microM) blocked Ang-II-mediated contraction, whereas in the CM contraction was resistant to indomethacin. Contractions caused by Ang-II in the CM preparations were also unaffected by inhibitors of leukotriene biosynthesis, but were partially (58%) inhibited by the cytochrome P450 monooxygenase inhibitor, ketoconazole. The diacylglycerol lipase inhibitor, U57,908, at a concentration (20 microM) that completely blocked the contractile action of epidermal growth factor in the LM, caused a substantial inhibition of Ang-II-mediated contraction in both the LM (55% inhibition) and CM (75% inhibition). The phospholipase A2 inhibitor, mepacrine caused a modest inhibition (24%) of contraction in both preparations. In the presence of U57,908, mepacrine further inhibited contraction caused by Ang-II in the LM preparation. The tyrosine kinase (YK) inhibitors, genistein and tyrphostin (RG 50864) selectively and completely blocked Ang-II-mediated contraction in the LM, without affecting contractions caused by carbachol and bradykinin. In the CM preparation, the two YK inhibitors were selective, but only partially (40-60%) blocked Ang-II-mediated contraction, without affecting contractions caused by bradykinin and carbachol.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗
Comparison of an endogenous protein kinase C substrate in rat aorta with rat brain MARCKS.
We have compared the properties of a rat aorta-derived protein kinase C substrate (p75) with those of 80 kDa kinase C substrates from rat brain (MARCKS) and rabbit aorta (p80). Rat aortic p75 appeared to be closely related to rat brain MARCKS on the basis of: solubility in perchloric acid and trichloroacetic acid, heat stability, isoelectric point (pI approximately 4.2), overall V8 protease phosphopeptide map, and immunocrossreactivity with an antibody directed against the N-terminal domain of MARCKS. However, p75 could be distinguished from rat brain MARCKS and from the rabbit aorta-derived p80 on the basis of its consistently more rapid electrophoretic mobility in SDS-containing gels, and in terms of a unique proteolytic phosphopeptide found in MARCKS but not in aortic p75. We conclude that p75 probably belongs to the family of protein kinase C substrates represented by MARCKS, and that differences in post-translational processing (glycosylation) or mRNA processing may account for the unique properties of the p75 protein in rat aortic tissue.
Animals↗
Synergistic actions of epidermal growth factor-urogastrone and vasopressin in cultured aortic A-10 smooth muscle cells.
In cultured rat aorta-derived A-10 cells, epidermal growth factor-urogastrone (EGF-URO) acts synergistically with arginine vasopressin (AVP) to augment the AVP-mediated release of 3H-arachidonate (3H-AA) from 3H-AA prelabeled cells. On its own, EGF-URO had no effect on AA release and had no effect on calcium influx or efflux either in the absence or presence of AVP. The synergistic action of EGF-URO was not affected by actinomycin D, cycloheximide, indomethacin, by the diacylglycerol lipase inhibitor U-57,908, or by the tyrosine kinase inhibitors genistein (GS) and tyrphostin (TP). TP did, nonetheless, completely abrogate 3H-thymidine incorporation triggered in the presence of EGF-URO. Although EGF-URO stimulated an increase in calpactin-II (lipocortin-I) phosphorylation in permeabilized cells, no such increase was detected in intact cells exposed to EGF-URO either alone or in combination with AVP, under conditions where EGF-URO augmented the action of AVP. The phospholipase A2 inhibitor, mepacrine, had no effect on AVP-mediated AA release, but abolished the synergistic action of EGF-URO. We conclude that in contrast with our previous results with gastric smooth muscle strips, wherein EGF-URO acts via the diacylglycerol lipase-mediated metabolism of diacylglycerol, and in keeping with observations with cultured mesangial cells, EGF-URO acts synergistically with AVP in A-10 cells via the activation of phospholipase A2. This synergistic action of EGF-URO does not appear to be due to increased levels of cyclooxygenase and would appear not to require increased tyrosine kinase activity.
Animals↗
Actions of thrombin and thrombin receptor peptide analogues in gastric and aortic smooth muscle: development of bioassays for structure-activity studies.
We have examined the biological activities of thrombin and the thrombin-receptor-related polypeptides, S42FLLRNPNDKYEPF55(TRP42-55), S42FLLRNPND50(TRP42-50), and A42FLLRNPND50(A42-TRP42-50) as well as an arginine-containing basic peptide beginning with the SF motif (SFRGHITR), in rat aortic (RA) rings and in a gastric guinea pig longitudinal (LM) smooth muscle preparation. In the RA preparation, thrombin, as well as the three receptor-related peptides caused a relaxation in tissue that was precontracted with noradrenaline; the basic peptide, SFRGHITR, was inactive either as an agonist or as an antagonist to TRP42-55. In the LM bioassay, which unlike the RA preparation did not persistently desensitize in response to thrombin, all three receptor-related peptides, like thrombin, caused a prompt phasic reproducible contraction. The basic peptide, SFRGHITR, was inactive. In the LM assay, TRP42-55, TRP42-50 and A42-TRP42-55 all caused comparable contractile responses. We conclude that the gastric LM smooth muscle possesses a thrombin receptor and provides a convenient and reliable assay for the activities of thrombin receptor-related peptides. Our data also demonstrated that neither the C-terminal hirudin-related pentapeptide nor the N-terminal serine hydroxyl group are required for the biological activity of the thrombin receptor-derived peptide previously described (TRP42-55). Based on our findings we suggest that only a small portion of the N-terminal sequence of TRP42-55 may be required for thrombin-like biological activity.
Amino Acid Sequence↗
Tyrosine kinase inhibitors and the contractile action of epidermal growth factor-urogastrone and other agonists in gastric smooth muscle.
We examined the effects of the tyrosine kinase (TK) inhibitors, genistein, and tyrphostin (RG-50864) on the contractile action of epidermal growth factor - urogastrone (EGF-URO), transforming growth factor-alpha (TGF-alpha), and other agonists in two smooth muscle bioassay systems (guinea pig gastric longitudinal muscle, LM, and circular muscle, CM). We also studied the inhibition by tyrphostin of EGF-URO stimulated protein phosphorylation in identical smooth muscle strips. The selective inhibition by genistein and tyrphostin of EGF-URO and TGF-alpha induced contraction, but not of carbachol- and bradykinin-mediated contraction, occurred at much lower concentrations (genistein, less than 7.4 microM (2 micrograms/mL); tyrphostin, less than 20 microM (4 micrograms/mL)) than those used in previously published studies with these TK inhibitors. In LM tissue, the IC50 values were for genistein 1.1 +/- 0.1 microM (0.30 micrograms/mL; mean +/- SEM) and 3.6 +/- 0.5 microM (0.74 micrograms/mL) for tyrphostin, yielding a molar potency ratio (GS: TP) of 1:3 in the longitudinal preparation. In CM tissue, the IC50 values were 3.0 +/- 0.3 microM (0.81 micrograms/mL) for genistein and 2.4 +/- 0.2 microM (0.49 micrograms/mL) for tyrphostin, yielding a molar potency ratio (GS:TP) of 1.0:0.8 in the circular strips. The inhibition by genistein and tyrphostin of EGF-URO and TGF-alpha mediated contraction was rapid (beginning within minutes) and was reversible upon washing the preparations free from the enzyme inhibitors. In intact tissue strips studied under bioassay conditions, tyrphostin (40 microM) also blocked EGF-URO triggered phosphorylation of substrates detected on Western blots using monoclonal antiphosphotyrosine antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Vascular actions of thrombin receptor peptide.
We have examined the action of the thrombin receptor-derived polypeptide, S42FLLRNPNDKYEPF55 (TRP 42-55), in rat and guinea pig aortic rings and helical arterial strips, and we have compared the actions of the peptide with those of thrombin. In rat preparations, both TRP 42-55 and thrombin caused a concentration-dependent endothelium-dependent relaxation that was blocked by N omega-nitro-L-arginine methyl ester; the relaxation response of the intact rat aortic strip preparation to concentrations of the peptide in the range 30-60 micrograms/mL (17-34 microM) was equivalent to the response to 0.03-0.1 U/mL of thrombin (about 0.3-0.9 nM), yielding a potency ratio (TRP 42-55:thrombin) of about 38,000:1. In contrast with the complete desensitization of thrombin-treated rat aortic preparations to a second administration of the enzyme, the rat aortic tissue was not desensitized by repeated exposures to TRP 42-55 and remained responsive to the peptide even after treatment of the tissue by thrombin. In contrast with the rat aortic tissue, in either intact or endothelium-free guinea pig aortic preparations both TRP 42-55 and thrombin caused a concentration-dependent endothelium-independent contraction. The contractile action of 60 micrograms/mL of receptor peptide (34 microM) in guinea pig aortic strip preparations was equivalent to the contractile action of 0.1-0.3 U/mL thrombin (0.9-3 nM), yielding a potency ratio of about 17,000:1. In guinea pig aortic preparations with an intact endothelium that were precontracted with noradrenaline, neither thrombin nor TRP42-55 caused relaxation, whereas substance P did so.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Action of thrombin receptor polypeptide in gastric smooth muscle: identification of a core pentapeptide retaining full thrombin-mimetic intrinsic activity.
We have used a guinea pig gastric longitudinal (LM) smooth muscle bioassay system to evaluate the contractile activities of a previously described thrombin receptor-derived polypeptide, S42FLLRNPNDKYEPF55 (one-letter amino acid code) (TRP42-55) and of a series of peptides derived from this sequence. The contractile activities of the polypeptides were compared with the actions of thrombin. Shortened peptides of the sequences S42FLLRNPND50, S42FLLRN47, and S42FLLR46 (TRP42-46) all exhibited contractile activities that were equivalent to or greater than those of the parent polypeptide, TRP42-55. Both TRP42-55 and TRP42-46 mimicked the action of thrombin, in terms of two different signal transduction pathways that were activated either in the LM preparation or in the related but distinct gastric circular muscle assay. In the LM preparation, the peptide FSLLR also exhibited appreciable, but much reduced, activity. Minimal activity was exhibited in the LM by the sequence SFLLA, but the lysine-containing analogue S42FLLK46 was about one fifth as potent as TRP42-46. In contrast, the receptor-derived sequences S42FLL45, S42FL44-NH2, F43LLR46, and S42ALLR46, as well as arginine-containing polypeptides beginning with the SF motif, SFRG and SFRGHITR, were inactive in the LM bioassay system, at concentrations of greater than or equal to 200 microM, as either agonists or antagonists against TRP42-55. In addition to its actions in the LM and circular muscle preparations, the active pentapeptide, TRP42-46, also exhibited thrombin-mimetic intrinsic activity in a rat aortic arterial ring relaxation bioassay, whereas the pentapeptide S42FLLA46 and the tetrapeptide S42FLL45 were inactive. We conclude that the intrinsic biological activity of the thrombin receptor-derived peptide resides in the pentapeptide TRP42-46 and that the phenylalanine and arginine residues at positions 43 and 46 play key roles in the activity of this pentapeptide in smooth muscle systems.
Amino Acid Sequence↗
Phosphorylation of aortic plasma membranes by protein kinase C.
Incubation of plasma membranes isolated from bovine aorta with either 0.5 mM CaCl2 or with a phorbol ester (1 microM phorbol 12,13-dibutyrate) and phosphatidylserine in an EGTA-containing buffer resulted in the phosphorylation of 10 proteins (Mr of 158, 105, 75, 62, 44, 39, 33, 22, 15 and 9 kDa), presumably due to activation of endogenous protein kinase C (PKC). After heat treatment of the aortic plasma membranes at 80 degrees C for 5 min in order to inactivate all endogenous protein kinase, phosphatase and ATPase activities, membrane phosphorylation was absolutely-dependent upon the addition of an exogenous, partially-purified PKC preparation from bovine aorta. Under these conditions, a total of 17 phosphoproteins could be detected (Mr of 158, 105, 75, 44, 39, 33, 30, 29, 27, 25, 22, 17.5, 16, 15, 11, 10 and 9 kDa). The most prominent phosphoprotein band in native membranes had a molecular weight of 75 kDa (p75); several characteristics suggest that p75 might be autophosphorylated PKC. The phosphorylation of aortic plasma membranes by exogenous PKC required phosphatidylserine and was calcium-dependent (10(-5) to 10(-7) M Ca2+); the addition of diolein resulted in little or no enhancement of phosphorylation. Replacement of phosphatidylserine with oleic acid resulted in the same number of phosphoproteins, but the extent of phosphorylation was diminished. The phosphorylation pattern was altered slightly if the aortic plasma membranes were isolated in the presence of 1 mM Ca2+ instead of EGTA buffers as in the standard procedure. Experiments were performed to determine if the p39 substrate of PKC in aortic plasma membranes was calpactin II (lipocortin I). Immunoblotting established that calpactin II was present in aortic plasma membranes, but there was no corresponding phosphoprotein on the autoradiographs.
Animals↗
Calmodulin inhibits the protein kinase C-catalysed phosphorylation of an endogenous protein in A10 smooth-muscle cells.
The protein kinase C (PKC) activator phorbol 12,13-dibutyrate stimulated the phosphorylation of a 75 kDa protein (p75) in intact cultured A10 smooth-muscle cells and sonicated cell preparations; p75 was the only major substrate for endogenous PKC in sonicated A10 cells. The Ca(2+)-dependent phosphorylation of p75 in vitro was dramatically decreased in PKC-down-regulated A10 cells; however, p75 from identical sonicated cell preparations was still phosphorylated by an exogenous aortic PKC preparation. Calmodulin inhibited the phosphorylation of p75 by PKC, but not the phosphorylation of other PKC substrates (platelet P47 protein and histone). The addition of calmodulin after the phosphorylation reaction was started prevented further phosphorylation, but did not decrease the extent of phosphorylation of p75 that was reached before the addition of calmodulin. The inhibition of p75 phosphorylation was concentration-dependent, with IC50 values (concn. giving 50% inhibition) ranging from less than 0.5 to 10 micrograms of calmodulin/ml, and was Ca(2+)-dependent, requiring a free Ca2+ concentration of 10 microM or greater. These results suggest that the inhibition of the PKC-catalysed phosphorylation of p75 by calmodulin may be due to its interaction with the substrate, rather than a direct inhibitory effect on the enzyme, and that this inhibition could be regulated by intracellular Ca2+ concentration. Therefore, p75 may be a physiological link between the PKC and Ca2+/calmodulin pathways.
Animals↗
Diacylglycerol lipase and the contractile action of epidermal growth factor-urogastrone: evidence for distinct signal pathways in a single strip of gastric smooth muscle.
In guinea pig gastric longitudinal muscle preparations, wherein epidermal growth factor-urogastrone (EGF-URO) causes contraction via the generation of arachidonate-derived prostaglandins, the specific diacylglycerol lipase (DG lipase) inhibitor, U57,908 (formerly designated RHC 80267) completely blocked EGF-URO and transforming growth factor-alpha (TGF-alpha)-mediated contraction, without affecting contractions caused by other agonists such as bradykinin, prostaglandin F2 alpha or arachidonic acid (AA). In contrast, the contractile actions of EGF-URO and TGF-alpha on the gastric circular muscle component, present in the same tissue strip as the longitudinal muscle preparation, were unaffected by concentrations of U57,908 that maximally inhibited contraction in the longitudinal muscle preparation. We conclude that in the longitudinal muscle preparation, EGF-URO acts not by the activation of phospholipase A2, but rather via the metabolism of diacylglycerol by DG lipase, thereby liberating arachidonic acid for the synthesis of contractile prostanoids. We also conclude that, even in the same tissue, the effects of EGF-URO on anatomically different components (longitudinal muscle versus circular muscle) can be mediated via two quite distinct signal transduction pathways.
Animals↗
Structure-activity relationships for transmembrane signaling: the receptor's turn.
The cloning, sequencing, and functional expression in host cells of a variety of receptors has led to a focus on the structural determinants of pharmacologic receptors involved in the complex processes of ligand binding and cell activation. The three basic mechanisms of receptor-mediated transmembrane signaling (ligand-regulated ion flux; ligand-regulated receptor-enzymes; ligand-regulated receptor-G protein activation) can now be placed in the structural context of at least three receptor superfamilies: 1) ligand-regulated oligomeric ion channels, 2) ligand-regulated tyrosine kinases, and 3) G protein-linked rhodopsin-related receptors. For each of these receptor superfamilies, structure-activity studies that use 1) site-directed mutagenesis, 2) cassette switching to form receptor chimeras, and 3) sequence-specific antireceptor antibodies are beginning to delineate the domains responsible for specific receptor functions. Analyses of such receptor domains related to: 1) ligand binding, 2) membrane insertion, 3) catalytic activity (in the case of receptor-enzymes), 4) internalization and interaction with other membrane constituents, 5) substrate or G protein binding, and 6) regulatory sites of receptor phosphorylation are discussed, using as principal examples the nicotinic receptor for acetylcholine, the epidermal growth factor-urogastrone receptor, and the beta-adrenergic receptor. These studies illustrate that in terms of structure-activity studies, which have traditionally emphasized the ligand, it is now the receptor's turn for intense attention.
Amino Acid Sequence↗
Distinct receptors for epidermal growth factor-urogastrone in cultured gastric smooth muscle cells.
We describe a propagable cell strain from guinea pig gastric circular muscle (GCM), which we have characterized in terms of its smooth muscle phenotype and its binding and biological response (thymidine incorporation) to epidermal growth factor-urogastrone (EGF-URO) and transforming growth factor-alpha (TGF-alpha). The binding of 125I-labeled EGF-URO to the GCM cells exhibited high affinity and an appropriate peptide specificity. A curvilinear Scatchard plot of the binding data indicated two classes of high-affinity binding sites (dissociation constants of 0.69 and 4.3 nM) and a maximal binding capacity of 24,000 sites/cell. Binding competition data demonstrated that the binding affinity of TGF-alpha was greater than that of EGF-URO by a factor of 2. These relative binding affinities agreed with the two- to threefold greater potency of TGF-alpha, compared with EGF-URO, for the stimulation of GCM thymidine incorporation. The relative order of binding affinity and biological potency (TGF-alpha greater than EGF-URO) was distinct from the relative order of binding affinities (EGF-URO greater than TGF-alpha) observed using guinea pig liver and human placental membrane preparations. We conclude that the cultured smooth muscle-derived GCM cells possess a receptor subtype that is in accord with contractile bioassay data obtained previously with intact gastric circular muscle strips. This receptor (TGF-alpha greater than EGF-URO) appears distinct from the one previously characterized in nonmuscle tissues.
Animals↗
Contraction of porcine ocular ciliary muscle by epidermal growth factor-urogastrone.
Epidermal growth factor-urogastrone (EGF) caused a concentration-dependent contractile response in porcine ocular ciliary muscle preparations. The half-maximal contraction was observed at 23 ng/ml EGF (4 nM). The contractile action of EGF, which was not abolished by the removal of extracellular calcium, was not affected by atropine, tetrodotoxin, phentolamine and indomethacin. In addition to causing contractions on its own, the contractile action of EGF was potentiated in the presence of prostaglandin E1 and vasopressin. Our data point to a potential role for EGF in the regulation of ciliary muscle tension.
Alprostadil↗
Contribution of the C-terminal dipeptide of transforming growth factor-alpha to its activity: biochemical and pharmacologic profiles.
We have used a matrix of biological (two distinct guinea-pig stomach contractile smooth muscle preparations) and biochemical (human placental membrane receptor binding and phosphorylation) assays to evaluate the activity profiles of epidermal growth factor-urogastrone (EGF-URO, mouse and human), transforming growth factor-alpha (TGF-alpha, human) and the TGF-alpha derivative lacking the C-terminal dipeptide, Leu49-Ala50, TGF-alpha-(1-48). In the longitudinal muscle (LM) bioassay, the relative potencies of the peptides were: EGF-URO greater than TGF-alpha greater than TGF-alpha-(1-48), with relative activity ratios (EC50S) of approximately 1:3:16. In the LM assay system, TGF-alpha-(1-48) was a partial agonist. In the circular muscle (CM) bioassay, the relative order of potencies was: TGF-alpha- greater than EGF-URO greater than TGF-alpha-(1-48), with EC50S of about 1:2:7. In the CM assay, all three peptides were full agonists, even though EGF-URO caused an intense desensitization of the tissue whereas TGF-alpha and TGF-alpha-(1-48) did not. The relative affinities of the peptides in the placenta membrane binding assay, EGF-URO greater than TGF-alpha greater than TGF-alpha-(1-48), were in good qualitative and quantitative agreement with the LM (but not the CM) bioassay, with relative KDS in the proportions of about 1:3:17. In the phosphorylation assay, using either the phosphorylated EGF-URO receptor or calpactin-II as an index of receptor kinase activation, the relative potencies of the peptides, EGF-URO greater than TGF-alpha greater than TGF-alpha-(1-48), were also qualitatively in accord with the relative potencies measured in the LM and ligand binding assays (but not in the CM preparation); however, quantitatively, the relative potency ratios (EC50S) observed in the phosphorylation assay (1:2:3) were somewhat out of keeping with the relative values observed in the LM and ligand binding assays. All three peptides were full agonists in the phosphorylation assay. Our data point to the importance of the C-terminal dipeptide, Leu49-Ala50 of TGF-alpha in terms of the binding affinity and intrinsic activity of this polypeptide; and our work provides further evidence for the distinct nature of the EGF-URO/TGF-alpha receptor system present in the CM bioassay preparation. The biological/biochemical activity profiles documented for the three polypeptides can serve as a basis for the further evaluation of other synthetic and naturally occurring members of the EGF-URO/TGF-alpha family of polypeptides.
Animals↗
Receptor triggering and receptor regulation: structure-activity relationships from the receptor's point of view.
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Animals↗
Phosphorylation of human placenta membrane calpactins with bovine brain protein kinase C.
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Animals↗